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Nature Looks at Yeast Gene Knockout Collection, 3D Profiling Approach, More

A description of the genomic alterations associated with the loss of nearly every single non-essential gene contained in the yeast Saccharomyces cerevisiae gene-knockout collection (YKOC) is presented in Nature this week. To build the resource, researchers sequenced the whole genomes of nearly all of the 4,732 strains comprising the homozygous diploid YKOC, extracting information on copy-number variation of tandem and interspersed repetitive DNA elements. An analysis of the resulting dataset "reveals genes that affect the maintenance of various genomic elements, highlights cross-talks between nuclear and mitochondrial genome stability, and shows how strains have genetically adapted to life in the absence of individual non-essential genes," they write. 

A technique for the simultaneous profiling of three-dimensional genome structure and DNA methylation in single human cells is reported in Nature Methods this week. A team from the Salk Institute for Biological Studies developed a single-nucleus methyl-3C sequencing technique to capture chromatin organization and DNA methylation information and separate heterogeneous cell types. They apply the approach to over 4,200 single human brain prefrontal cortex cells and reconstruct cell-type specific chromatin conformation maps from 14 cortical cell types. Their data reveal the genome-wide association between "cell-type specific chromatin conformation and differential DNA methylation, suggesting pervasive interactions between epigenetic processes regulating gene expression."

Scientists from the University of Wisconsin, Madison have developed a new biodegradable nanocapsule that can be used to trigger CRISPR genome editing in vivo, they report in this week's Nature Nanotechnology. The researchers synthesized a thin glutathione-cleavable covalently crosslinked polymer coating around a preassembled ribonucleoprotein complex between a Cas9 nuclease and a single-guide RNA. The nanocapsules were found to not only generate targeted gene edits in vitro without any apparent toxicity, but produced robust gene editing when delivered locally to retinal pigment epithelium tissue and skeletal muscle in mice.

The effects of prolonged early-life antibiotic exposure can be observed in the microbiomes of infants long after treatment is finished, according to a study in Nature Microbiology. Scientists used a combination of metagenomic, culture-based, and machine learning techniques to study the gut microbiota and resistome of antibiotic-exposed preterm infants during and after hospitalization. A comparison with antibiotic-naive healthy infants reveals a persistently enriched gastrointestinal antibiotic resistome, prolonged carriage of multidrug-resistant Enterobacteriaceae, and distinct antibiotic-driven patterns of microbiota and resistome assembly in extremely preterm infants who received antibiotic treatment. "The collateral damage of early-life antibiotic treatment and hospitalization in preterm infants is long lasting," the researchers write. "We urge the development of strategies to reduce these consequences in highly vulnerable neonatal populations."